This is an application for a K23 award for Dr. Jean Tang, a dermatologist at the University of California, San Francisco. Dr. Tang is establishing herself as a young investigator in patient-oriented, translational research in the prevention of basal cell carcinoma (BCC). This K23 award will provide Dr. Tang with the support necessary to accomplish the following goals: (1) to conduct a mouse preclinical trial on vitamin D for BCC prevention; (2) to conduct secondary data analysis in a large prospective cohort of senior men that have baseline vitamin D measurements; (3) to conduct a pilot clinical trial in humans to test the feasibility of topical or oral vitamin D3. To achieve these goals, Dr. Tang has assembled a mentoring team comprised of a primary mentor, Dr. Ervin Epstein, Scientist at Children's Hospital of Oakland Research Institute, who conducts laboratory and clinical trials in chemoprevention of BCC, and three co-mentors: Dr. Steven Cummings, Director of the San Francisco Coordinating Center who is an expert in clinical studies and trials of large patient cohorts; Dr. Mary-Margaret Chren, an expert in dermatology outcomes research; and Dr. Charles McCullough, who has expertise in longitudinal data analysis and biostatistics. Currently, there is no effective agent to prevent basal cell carcinomas (BCC). Sunscreens have not been shown to prevent BCC; however, recent in vitro data suggests that vitamin D3 inhibits the aberrant signaling pathway found in BCC. Dr. Tang has shown that topical application of vitamin D3 in mice will prevent 50% of BCCs. In this K23, she proposes to determine the optimal route of delivery of vitamin D3 for inhibition of BCC in mice (Aim 1) and to determine whether high levels of serum vitamin D reduce BCC risk in senior men (Aim 2). Dr. Tang will also conduct a pilot clinical trial to test the feasibility of topical and oral vitamin D3 in patients with basal cell nevus syndrome who have multiple BCCs (Aim 3). From the mouse preclinical trial and the human pilot trial, we will determine the optimal administration of vitamin D3 for inhibition of a biomarker of BCC. These results will provide critical preliminary data for a randomized controlled clinical trial using vitamin D3 for prevention of BCC tumors in Basal Cell Nevus Syndrome patients, which will be developed during the K award and submitted as a R34 grant application to the NIH at the end of Year 5. RELEVANCE (See instructions): Sunscreens do not prevent basal cell carcinomas of the skin, the most common cancer found in the US. Our goal is to determine whether vitamin D is an effective and safe agent to prevent basal cell carcinomas.